Induction of anti-tumor immunity elicited by tumor cells expressing a murine LFA-3 analog via a recombinant vaccinia virus

T cell activation requires binding of the T cell receptor to the major hist ocompatibility molecule-peptide complex in the presence of adhesion and/or costimulatory molecules such as B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), an d CD2. The major ligand of CD2 is CD48, the murine analog of human leukocyt e function-associated antigen 3 (LFA-3). To determine the effect of LFA-3 e xpression on the immunogenicity of tumor cells, we constructed a recombinan t vaccinia virus containing the murine LFA-3 gene (designated rV-LFA-3). rV LFA-3 was shown to be functional in vitro in terms of expression of LFA-3, T cell proliferation, adhesion, and cytotoxicity. Subcutaneous inoculation of rV-LFA-3-infected murine colon adenocarcinoma tumor cells (MC38) into im munocompetent syngeneic C57BL/6 mice resulted in complete lack of tumor gro wth. Inoculation of MC38 cells infected with equal doses of control wild-ty pe vaccinia virus resulted in tumor growth in all animals. In addition, par tial immunological protection was demonstrated against subsequent challenge with uninfected parental tumor cells up to 56 days after vaccination with rV-LFA-3-infected cells, Anti-tumor memory was also demonstrated by using g amma-irradiated MC38 cells and cells from another carcinoma model (CT26), T hese studies demonstrate that expression of LFA-3 via a poxvirus vector can be used to induce antitumor immunity.